Repeated intracerebroventricular administration of β-amyloid25-35 to rats decreases muscarinic receptors in cerebral cortex

The effects of repeated in vivo administration to rats of beta-amyloid(25-35) (beta A(25-35)) on several cholinergic markers have been studied and compared with those of a peptide with a scrambled sequence, Rats received intracerebroventricular injections of beta A(25-35) (5 Or 20 mu g/day) for 7 days and they were sacrificed at 2 or 3 weeks survival. The density of total muscarinic receptors labeled with [H-3] N-methyl-scopolamine was dose-dependently decreased by beta A(25-35) in the cerebral cortex at 3 weeks survival. No changes were observed at 2 weeks survival in cerebral cortex or in the hippocampus, at any time. beta A(25-35) administration did not modify choline acetyltranferase activity in cerebral cortex. However, in beta A(25-35)-treated rats hypertrophic/hyperactive positive acetylcholinesterase nucleus basalis cholinergic neurons were observed at 2 weeks survival, while the density of acetylcholinesterase-positive fibers of cerebral cortex was increased along with the number. of cortical positive neurons at 3 weeks survival. These results suggest that increased cholinergic function may be responsible of muscarinic receptor down-regulation. Given the involvement of cholinergic systems in memory and learning, repeated administration of beta A(25-35) may represent a good approach to explore the role of PA in Alzheimer's disease and to develop therapeutic strategies relevant to it. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.